Neovacular Age-related Macular Degeneration
Conditions
Keywords
nAMD, VEGF, VEGF agent, BCVA, CRT, Ranibizumab, Lucentis, Aflibercept, Eylea
Brief summary
This study assessed systemic vascular endothelial growth factor (VEGF) level in patients with neovascular Age-related Macular Degeneration following treatment with Ranibizumab or Aflibercept. Free plasma VEGF-A level was measured in this study .
Interventions
PROCEDURENeovascular Age-related Macular Degeneration
Blood measurement
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria * Newly diagnosed Age-related Macular Degeneration (AMD) * No previous treatment received for diagnosed AMD * Visual Acuity 6/7.5 to 6/96 Key
Exclusion criteria
* standard
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline at Month 3 in Plasma VEGF Following Intravitreal (IVT) Injection of Anti-VEGF Agent | Change from baseline at Month 3 | Percent change in blood VEGF level is calculated as the difference in blood VEGF level measured after 3 month of anti-VEGF agent IVT treatment (Ranibizumab or Aflibercept) when compared to baseline blood VEGF level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Plasma VEGF Level Overtime | Change from baseline up to month 3 | Plasma VEGF measurement performed at all visits and compared to baseline level |
| Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime | pre-dose to post-dose at Baseline, week 1, week 2, month 1, month 2, and month 3 | VEGF level and anti-VEGF concentration measured in the blood at each single visit, including pre- and post-dose measurement at the dosing visits. |
| Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye Over Time | Baseline, month 1, month 2, month 3 | BCVA score is assessed on study eye based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity charts at a testing distance of 4 meters. An increase in score indicates an improvement in acuity. Change from baseline calculated as observed post-baseline value - baseline value. |
| Mean Change From Baseline in Central Retinal Thickness (CRT) of the Study Eye Over Time | Baseline, month 1, month 2, month 3 | CRT in micrometers assessed by Optical Tomography (OCT) at each single study visit. A reduction is thickness indicates an improvement is the lesion area. Change from baseline calculated as observed post-baseline - baseline value. |
| Number of Patients With Ocular and Systemic Adverse Events | Day 1 to day 85 | The incidence of reported treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAE). |
Countries
Israel, Malaysia, Philippines, Singapore, South Korea, Taiwan, Thailand
Participant flow
Recruitment details
All randomized patients were included in the Full Analysis Set (FAS).
Participants by arm
| Arm | Count |
|---|---|
| Ranibizumab 104 patients with an eligible study eye were randomized to be treated with Ranibizumab IVT. 0.5 mg of commercially available Ranibizumab were used for intravitreal injection administered by an unblinded injecting physician. 3 injections were performed (Baseline, Month 1, Month 2). | 104 |
| Aflibercept 101 patients with an eligible study eye were randomized to be treated with Aflibercept IVT. 2.0 mg of commercially available Aflibercept were used for intravitreal injection administered by an unblinded injecting physician. 3 injections were performed (Baseline, Month 1, Month 2). | 101 |
| Total | 205 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Subject/guardian decision | 1 | 1 |
Baseline characteristics
| Characteristic | Ranibizumab | Aflibercept | Total |
|---|---|---|---|
| Age, Continuous | 70.1 Years STANDARD_DEVIATION 9 | 72.0 Years STANDARD_DEVIATION 8.43 | 71.0 Years STANDARD_DEVIATION 8.76 |
| Sex: Female, Male Female | 42 Participants | 44 Participants | 86 Participants |
| Sex: Female, Male Male | 62 Participants | 57 Participants | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 104 | 19 / 101 | 39 / 205 |
| serious Total, serious adverse events | 3 / 104 | 5 / 101 | 8 / 205 |
Outcome results
Primary
Percent Change From Baseline at Month 3 in Plasma VEGF Following Intravitreal (IVT) Injection of Anti-VEGF Agent
Percent change in blood VEGF level is calculated as the difference in blood VEGF level measured after 3 month of anti-VEGF agent IVT treatment (Ranibizumab or Aflibercept) when compared to baseline blood VEGF level.
Time frame: Change from baseline at Month 3
Population: Full Analysis Set (FAS): The FAS consisted of all randomized patients who received at least one dose of study treatment. FAS was the analysis set. However, patients who were randomized due to erroneous use of the IRT system and who did not receive at least one dose of study treatment were excluded from the FAS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab | Percent Change From Baseline at Month 3 in Plasma VEGF Following Intravitreal (IVT) Injection of Anti-VEGF Agent | 41.04 Percent change | Standard Error 19.918 |
| Aflibercept | Percent Change From Baseline at Month 3 in Plasma VEGF Following Intravitreal (IVT) Injection of Anti-VEGF Agent | -21.53 Percent change | Standard Error 20.398 |
Comparison: H0: μR = μA versus HA: μR ≠ μAp-value: 0.01295% CI: [13.96, 111.17]Mixed Models Analysis
Secondary
Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime
VEGF level and anti-VEGF concentration measured in the blood at each single visit, including pre- and post-dose measurement at the dosing visits.
Time frame: pre-dose to post-dose at Baseline, week 1, week 2, month 1, month 2, and month 3
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ranibizumab | Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime | Month 1 (post-IVT injection) | -0.110 pearson correlation coefficient |
| Ranibizumab | Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime | Month 2 (pre-IVT injection) | -0.151 pearson correlation coefficient |
| Ranibizumab | Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime | Month 2 (post-IVT injection) | -0.049 pearson correlation coefficient |
| Ranibizumab | Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime | Month 3 | -0.047 pearson correlation coefficient |
| Ranibizumab | Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime | Baseline (post-IVT injection) | -0.141 pearson correlation coefficient |
| Ranibizumab | Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime | Week 1 | 0.027 pearson correlation coefficient |
| Ranibizumab | Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime | Week 2 | -0.085 pearson correlation coefficient |
| Ranibizumab | Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime | Month 1 (pre-IVT injection) | -0.065 pearson correlation coefficient |
| Aflibercept | Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime | Month 1 (pre-IVT injection) | 0.127 pearson correlation coefficient |
| Aflibercept | Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime | Month 1 (post-IVT injection) | 0.088 pearson correlation coefficient |
| Aflibercept | Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime | Baseline (post-IVT injection) | 0.083 pearson correlation coefficient |
| Aflibercept | Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime | Month 2 (pre-IVT injection) | 0.051 pearson correlation coefficient |
| Aflibercept | Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime | Week 2 | 0.192 pearson correlation coefficient |
| Aflibercept | Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime | Month 2 (post-IVT injection) | 0.098 pearson correlation coefficient |
| Aflibercept | Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime | Week 1 | 0.234 pearson correlation coefficient |
| Aflibercept | Correlation Between Percent Change From Baseline Plasma VEGF Level and the Serum Anti-VEGF Agent Overtime | Month 3 | 0.229 pearson correlation coefficient |
Secondary
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye Over Time
BCVA score is assessed on study eye based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity charts at a testing distance of 4 meters. An increase in score indicates an improvement in acuity. Change from baseline calculated as observed post-baseline value - baseline value.
Time frame: Baseline, month 1, month 2, month 3
Population: FAS: The FAS consisted of all randomized patients who received at least one dose of study treatment. FAS was the analysis set. However, patients who were randomized due to erroneous use of the IRT system and who did not receive at least one dose of study treatment were excluded from the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye Over Time | Change at month 1 (n= 99, 100) | 3.9 Letter | Standard Deviation 7.45 |
| Ranibizumab | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye Over Time | Change at month 2 (n=98, 99) | 5.8 Letter | Standard Deviation 8.54 |
| Ranibizumab | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye Over Time | Change at month 3 (n= 99, 99) | 6.1 Letter | Standard Deviation 8.36 |
| Aflibercept | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye Over Time | Change at month 2 (n=98, 99) | 5.1 Letter | Standard Deviation 9.72 |
| Aflibercept | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye Over Time | Change at month 3 (n= 99, 99) | 6.9 Letter | Standard Deviation 11.68 |
| Aflibercept | Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye Over Time | Change at month 1 (n= 99, 100) | 2.8 Letter | Standard Deviation 9.7 |
Secondary
Mean Change From Baseline in Central Retinal Thickness (CRT) of the Study Eye Over Time
CRT in micrometers assessed by Optical Tomography (OCT) at each single study visit. A reduction is thickness indicates an improvement is the lesion area. Change from baseline calculated as observed post-baseline - baseline value.
Time frame: Baseline, month 1, month 2, month 3
Population: FAS: The FAS consisted of all randomized patients who received at least one dose of study treatment. FAS was the analysis set. However, patients who were randomized due to erroneous use of the IRT system and who did not receive at least one dose of study treatment were excluded from the FAS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab | Mean Change From Baseline in Central Retinal Thickness (CRT) of the Study Eye Over Time | Change at month 1 (n= 101, 100) | -75.0 micrometers | Standard Deviation 91.04 |
| Ranibizumab | Mean Change From Baseline in Central Retinal Thickness (CRT) of the Study Eye Over Time | Change at month 2 (n= 100, 99) | -94.3 micrometers | Standard Deviation 103.41 |
| Ranibizumab | Mean Change From Baseline in Central Retinal Thickness (CRT) of the Study Eye Over Time | Change at month 3 (n= 100, 99) | -93.7 micrometers | Standard Deviation 110.41 |
| Aflibercept | Mean Change From Baseline in Central Retinal Thickness (CRT) of the Study Eye Over Time | Change at month 1 (n= 101, 100) | -93.8 micrometers | Standard Deviation 106.43 |
| Aflibercept | Mean Change From Baseline in Central Retinal Thickness (CRT) of the Study Eye Over Time | Change at month 2 (n= 100, 99) | -116.6 micrometers | Standard Deviation 123.35 |
| Aflibercept | Mean Change From Baseline in Central Retinal Thickness (CRT) of the Study Eye Over Time | Change at month 3 (n= 100, 99) | -124.3 micrometers | Standard Deviation 122.46 |
Secondary
Number of Patients With Ocular and Systemic Adverse Events
The incidence of reported treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAE).
Time frame: Day 1 to day 85
Population: Safety (SAF) analysis set: The SAF analysis set included all patients who received at least one dose of study treatment and had at least one post-baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ranibizumab | Number of Patients With Ocular and Systemic Adverse Events | TEAEs | 32 Participants |
| Ranibizumab | Number of Patients With Ocular and Systemic Adverse Events | TESAEs | 3 Participants |
| Ranibizumab | Number of Patients With Ocular and Systemic Adverse Events | TEAEs leading to death | 0 Participants |
| Ranibizumab | Number of Patients With Ocular and Systemic Adverse Events | TEAEs with suspected relationship to study drug | 6 Participants |
| Ranibizumab | Number of Patients With Ocular and Systemic Adverse Events | TESAEs with suspected relationship to study drug | 1 Participants |
| Ranibizumab | Number of Patients With Ocular and Systemic Adverse Events | TEAEs w/ suspected relationship to ocular inject. | 12 Participants |
| Ranibizumab | Number of Patients With Ocular and Systemic Adverse Events | TESAEs w/ suspected relationship to ocular inject. | 1 Participants |
| Ranibizumab | Number of Patients With Ocular and Systemic Adverse Events | TEAEs leading to disc. of study treatment | 3 Participants |
| Aflibercept | Number of Patients With Ocular and Systemic Adverse Events | TEAEs leading to disc. of study treatment | 1 Participants |
| Aflibercept | Number of Patients With Ocular and Systemic Adverse Events | TEAEs | 32 Participants |
| Aflibercept | Number of Patients With Ocular and Systemic Adverse Events | TESAEs with suspected relationship to study drug | 0 Participants |
| Aflibercept | Number of Patients With Ocular and Systemic Adverse Events | TESAEs | 5 Participants |
| Aflibercept | Number of Patients With Ocular and Systemic Adverse Events | TESAEs w/ suspected relationship to ocular inject. | 0 Participants |
| Aflibercept | Number of Patients With Ocular and Systemic Adverse Events | TEAEs with suspected relationship to study drug | 4 Participants |
| Aflibercept | Number of Patients With Ocular and Systemic Adverse Events | TEAEs leading to death | 0 Participants |
| Aflibercept | Number of Patients With Ocular and Systemic Adverse Events | TEAEs w/ suspected relationship to ocular inject. | 11 Participants |
Secondary
Percent Change From Baseline in Plasma VEGF Level Overtime
Plasma VEGF measurement performed at all visits and compared to baseline level
Time frame: Change from baseline up to month 3
Population: FAS: The FAS consisted of all randomized patients who received at least one dose of study treatment. FAS was the analysis set. However, patients who were randomized due to erroneous use of the IRT system and who did not receive at least one dose of study treatment were excluded from the FAS.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ranibizumab | Percent Change From Baseline in Plasma VEGF Level Overtime | Month 1 (post-IVT injection; n=101, 100) | 12.27 Percent change | Standard Error 6.711 |
| Ranibizumab | Percent Change From Baseline in Plasma VEGF Level Overtime | Week 1 (n=103, 101) | 44.08 Percent change | Standard Error 14.377 |
| Ranibizumab | Percent Change From Baseline in Plasma VEGF Level Overtime | Month 2 (pre-IVT injection; n=100, 99) | 10.78 Percent change | Standard Error 7.342 |
| Ranibizumab | Percent Change From Baseline in Plasma VEGF Level Overtime | Baseline (post-IVT injection; n=104, 100) | 11.93 Percent change | Standard Error 5.836 |
| Ranibizumab | Percent Change From Baseline in Plasma VEGF Level Overtime | Month 2 (post-IVT injection; n=100, 99) | 50.59 Percent change | Standard Error 19.076 |
| Ranibizumab | Percent Change From Baseline in Plasma VEGF Level Overtime | Week 2 (n=102, 100) | 38.76 Percent change | Standard Error 11.165 |
| Ranibizumab | Percent Change From Baseline in Plasma VEGF Level Overtime | Month 3 (n=100, 99) | 41.04 Percent change | Standard Error 19.918 |
| Ranibizumab | Percent Change From Baseline in Plasma VEGF Level Overtime | Month 1 (pre-IVT injection; n= 102, 100)) | 112.05 Percent change | Standard Error 60.182 |
| Aflibercept | Percent Change From Baseline in Plasma VEGF Level Overtime | Month 3 (n=100, 99) | -21.53 Percent change | Standard Error 20.398 |
| Aflibercept | Percent Change From Baseline in Plasma VEGF Level Overtime | Month 1 (pre-IVT injection; n= 102, 100)) | 23.12 Percent change | Standard Error 61.641 |
| Aflibercept | Percent Change From Baseline in Plasma VEGF Level Overtime | Baseline (post-IVT injection; n=104, 100) | -9.37 Percent change | Standard Error 6.1 |
| Aflibercept | Percent Change From Baseline in Plasma VEGF Level Overtime | Week 1 (n=103, 101) | -7.44 Percent change | Standard Error 14.722 |
| Aflibercept | Percent Change From Baseline in Plasma VEGF Level Overtime | Week 2 (n=102, 100) | -16.45 Percent change | Standard Error 11.434 |
| Aflibercept | Percent Change From Baseline in Plasma VEGF Level Overtime | Month 1 (post-IVT injection; n=101, 100) | -20.61 Percent change | Standard Error 6.861 |
| Aflibercept | Percent Change From Baseline in Plasma VEGF Level Overtime | Month 2 (pre-IVT injection; n=100, 99) | -19.13 Percent change | Standard Error 7.519 |
| Aflibercept | Percent Change From Baseline in Plasma VEGF Level Overtime | Month 2 (post-IVT injection; n=100, 99) | -16.09 Percent change | Standard Error 19.535 |